1. miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis.
- Author
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Meng, Fanyi, Yang, Man, Chen, Yinshuang, Chen, Weichang, and Wang, Weipeng
- Subjects
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COLORECTAL cancer , *IMMUNE checkpoint proteins , *SIRTUINS , *IMMUNOSUPPRESSION - Abstract
Although a number of studies have revealed the important roles of miR-34a in cancer, the regulatory roles of miR-34a in cancer immune response remain largely unknown. Our present study demonstrated a mechanism underlying miR-34a-mediated cancer immune evasion via a SIRT1/NF-κB/B7-H3/TNF-α axis. miR-34a upregulated B7-H3, an important immune checkpoint molecule, through direct inhibition of SIRT1 and consequent acetylation of NF-κB subunit p65 (a-p65), which promoted B7-H3 transcription by direct binding to its promoter. The elevated B7-H3 induced production of pro-inflammatory cytokines including TNF-α. This was further confirmed in the colon of Mir34a-deficient mice, where Sirt1 expression was boosted, and the expressions of a-p65, B7h3, and Tnf were repressed. Consequently, the in vivo inhibitory activity of miR-34a on colorectal cancer (CRC) was eradicated by the reinforced B7-H3 and TNF-α. In conclusion, our study uncovered an etiological mechanism underlying miR-34a-mediated CRC immune evasion through inhibition of SIRT1 and promotion of NF-κB/B7-H3/TNF-α axis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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